References of "Willems, Luc"
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See detailLe BLV: un modele d'etude pour les leucemies humaines.
Willems, Luc ULg

in Bulletin et Mémoires de l'Académie Royale de Médecine de Belgique (2004), 159(10-12),

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See detailInvestigation of the susceptibility of human cell lines to bovine herpesvirus 4 infection: Demonstration that human cells can support a nonpermissive persistent infection which protects them against tumor necrosis factor alpha-induced apoptosis
Gillet, Laurent ULg; Minner, F.; Detry, Bruno et al

in Journal of Virology (2004), 78(5), 2336-2347

Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus that has a worldwide distribution in the population of cattle. Many factors make human contamination by BoHV-4 likely to occur. In this study, we ... [more ▼]

Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus that has a worldwide distribution in the population of cattle. Many factors make human contamination by BoHV-4 likely to occur. In this study, we performed in vitro experiments to assess the risk and the consequences of human infection by BoHV-4. First, by using a recombinant BoHV-4 strain expressing enhanced green fluorescent protein under the control of the human cytomegalovirus immediate-early gene promoter, we tested 21 human cell lines for their sensitivity and their permissiveness to BoHV-4 infection. These experiments revealed that human cell lines from lymphoid and myeloid origins were resistant to infection, whereas epithelial cells, carcinoma cells, or adenocarcinoma cells isolated from various organs were sensitive but poorly permissive to BoHV-4 infection. Second, by using the HeLa cell line as a model of human cells sensitive but not permissive to BoHV-4 infection, we investigated the resistance of infected cells to apoptosis and the persistence of the infection through cellular divisions. The results obtained can be summarized as follows. (i) BoHV-4 nonpermissive infection of HeLa cells protects them against tumor necrosis factor alpha-induced apoptosis. (ii) BoHV-4 infection of HeLa cells persists in cell culture; however, the percentage of infected cells decreases with time due to erratic transmission of the viral genome through cell division. (iii) BoHV-4 infection has no effect on the rate of HeLa cell division. Altogether, these data suggest that BoHV-4 could infect humans. This study also stresses the importance of considering the insidious effects of nonpermissive infection when the biosafety of animal gammaherpesviruses for humans is being considered. [less ▲]

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See detailSuppression Of Tumor Growth And Cell Proliferation By P13(Ii), A Mitochondrial Protein Of Human T Cell Leukemia Virus Type 1
Silic-Benussi, M.; Cavallari, L.; Zorzan, T. et al

in Proceedings of the National Academy of Sciences of the United States of America (2004), 101(17),

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See detailReduced proviral loads during primo-infection of sheep by Bovine Leukemia virus attenuated mutants.
Debacq, Christophe; Sanchez Alcaraz, Maria Teresa; Mortreux, Franck et al

in Retrovirology (2004), 1(1),

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See detailInteraction of retroviral Tax oncoproteins with tristetraprolin and regulation of tumor necrosis factor-alpha expression.
Twizere, Jean-Claude ULg; Kruys, Veronique; Lefebvre, Laurent et al

in Journal of the National Cancer Institute (2003), 95(24), 1846-59

BACKGROUND: The Tax oncoproteins are transcriptional regulators of viral expression involved in pathogenesis induced by complex leukemogenic retroviruses (or delta-retroviruses, i.e., primate T-cell ... [more ▼]

BACKGROUND: The Tax oncoproteins are transcriptional regulators of viral expression involved in pathogenesis induced by complex leukemogenic retroviruses (or delta-retroviruses, i.e., primate T-cell leukemia viruses and bovine leukemia virus). To better understand the molecular pathways leading to cell transformation, we aimed to identify cellular proteins interacting with Tax. METHODS: We used a yeast two-hybrid system to identify interacting cellular proteins. Interactions between Tax and candidate interacting cellular proteins were confirmed by glutathione S-transferase (GST) pulldown assays, co-immunoprecipitation, and confocal microscopy. Functional interactions between Tax and one interacting protein, tristetraprolin (TTP), were assessed by analyzing the expression of tumor necrosis factor-alpha (TNF-alpha), which is regulated by TTP, in mammalian cells (HeLa, D17, HEK 293, and RAW 264.7) transiently transfected with combinations of intact and mutant Tax and TTP. RESULTS: We obtained seven interacting cellular proteins, of which one, TTP, was further characterized. Tax and TTP were found to interact specifically through their respective carboxyl-terminal domains. The proteins colocalized in the cytoplasm in a region surrounding the nucleus of HeLa cells. Furthermore, coexpression of Tax was associated with nuclear accumulation of TTP. TTP is an immediate-early protein that inhibits expression of TNF-alpha at the post-transcriptional level. Expression of Tax reverted this inhibition, both in transient transfection experiments and in stably transfected macrophage cell lines. CONCLUSION: Tax, through its interactions with the TTP repressor, indirectly increases TNF-alpha expression. This observation is of importance for the cell transformation process induced by leukemogenic retroviruses, because TNF-alpha overexpression plays a central role in pathogenesis. [less ▲]

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See detailReduced Cell Turnover In Bovine Leukemia Virus-Infected, Persistently Lymphocytotic Cattle
Debacq, C.; Asquith, B.; Reichert, M. et al

in Journal of Virology (2003), 77(24),

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See detailIncreased cell proliferation-but not reduced cell death-induces lymphocytosis in Bovine Leukaemia Virus-infected sheep
Debacq, Christophe; Asquith, B.; Kerkhofs, Pierre et al

in Abstracts of papers presented at the 2002 meeting of retroviruses (2002, May)

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See detailInteracting surface of the receptor-binding domain.
Gatot, Jean-Stéphane; Callebaut, Isabelle; Van Lint, Carine et al

in Société Belge de Biochimie et de Biologie moléculaire. (2002, February 22)

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See detailIn vivo cell turnover in BLV-infected sheep.
Debacq, Christophe; Asquith, B.; Kerkhofs, Pierre et al

in Société Belge de Biochimie et de Biologie moléculaire (2002, February 22)

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See detailOncoviral bovine leukemia virus G4 and human T-cell leukemia virus type 1 p13(II) accessory proteins interact with farnesyl pyrophosphate synthetase
Lefebvre, Laurent; Vanderplasschen, Alain ULg; Ciminale, Vincenzo et al

in Journal of Virology (2002), 76(3), 1400-1414

G4 and p13(II) are accessory proteins encoded by the X region of bovine leukemia virus and human T-cell leukemia virus type 1 (HTLV-1), respectively. Disruption of the G4 and p13(II) open reading frames ... [more ▼]

G4 and p13(II) are accessory proteins encoded by the X region of bovine leukemia virus and human T-cell leukemia virus type 1 (HTLV-1), respectively. Disruption of the G4 and p13(II) open reading frames interferes with viral spread in animal model systems, indicating that the corresponding proteins play a key role in viral replication. In addition, G4 is oncogenic in primary cell cultures and is absolutely required for efficient onset of leukemogenesis in sheep. To gain insight into the function of these proteins, we utilized the yeast two-hybrid system to identify protein partners of G4. Results revealed that G4 interacts with farnesyl pyrophosphate synthetase (FPPS), a protein involved in the mevalonate/squalene pathway and in synthesis of FPP, a substrate required for prenylation of Ras. The specificity of the interaction was verified by glutathione S-transferase (GST) pull-down assays and by coimmunoprecipitation experiments. Furthermore, confocal microscopy showed that the subcellular localization of G4 was profoundly affected by FPPS. The G4 protein itself was not prenylated, at least in rabbit reticulocyte lysate-based assays. The domain of G4 required for binding to FPPS was restricted to an amphipathic alpha-helix rich in arginine residues. Subtle mutation of this alpha-helix abrogated G4 oncogenic potential in vitro, providing a biological relevance for FPPS-G4 complex formation in cells. Finally, HTLV-1 p13(II) was also found to specifically interact with FPPS (in yeast as well as in GST pull-down assays) and to colocalize with G4 in mitochondria, suggesting a functional analogy between these oncoviral accessory proteins. Identification of FPPS as a molecular partner for p13(II) and G4 accessory proteins opens retrovirus-induced leukemia. [less ▲]

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See detailBovine Leukemia Virus Su Protein Interacts With Zinc, And Mutations Within Two Interacting Regions Differentially Affect Viral Fusion And Infectivity In Vivo
Gatot, Js.; Callebaut, I.; Van Lint, C. et al

in Journal of Virology (2002), 76(16),

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See detailSubcellular Localization Of The Bovine Leukemia Virus R3 And G4 Accessory Proteins
Lefebvre, Laurent; Ciminale, Vincenzo; Vanderplasschen, Alain ULg et al

in Journal of Virology (2002), 76(15), 7843-7854

Bovine leukemia virus (BLV) is a complex retrovirus that belongs to the Deltaretrovirus genus, which also includes Human T-cell leukemia virus type 1 (HTLV-1). Both viruses contain an X region coding for ... [more ▼]

Bovine leukemia virus (BLV) is a complex retrovirus that belongs to the Deltaretrovirus genus, which also includes Human T-cell leukemia virus type 1 (HTLV-1). Both viruses contain an X region coding for at least four proteins: Tax and Rex, which are involved in transcriptional and posttranscriptional regulation, respectively, and the accessory proteins R3 and G4 (for BLV) and p12(I), p13(II), and p30(II) (for HTLV-1). The present study was aimed at characterizing the subcellular localization of BLV R3 and G4. The results of immunofluorescence experiments on transfected HeLa Tat cells demonstrated that R3 is located in the nucleus and in cellular membranes, as previously reported for HTLV-1 p12(1). In contrast, G4, like p13(II), is localized both in the nucleus and in mitochondria. In addition, we have shown that G4 harbors a mitochondrial targeting signal consisting of a hydrophobic region and an amphipathic alpha-helix. Thus, despite a lack of significant primary sequence homology, R3 and p12(1) and G4 and p13(II) exhibit similar targeting properties, suggesting possible overlap in their functional properties. [less ▲]

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See detailLymphocyte Kinetics: The Interpretation Of Labelling Data
Asquith, B.; Debacq, C.; Macallan, Dc. et al

in Trends In Immunology (2002), 23(12),

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See detailInhibition Of Histone Deacetylases Induces Bovine Leukemia Virus Expression In Vitro And In Vivo
Merezak, C.; Reichert, M.; Van Lint, C. et al

in Journal of Virology (2002), 76(10),

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See detailIncreased Cell Proliferation, But Not Reduced Cell Death, Induces Lymphocytosis In Bovine Leukemia Virus-Infected Sheep
Debacq, C.; Asquith, B.; Kerkhofs, P. et al

in Proceedings of the National Academy of Sciences of the United States of America (2002), 99(15),

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See detailCell turnover in BLV-infected sheep
Debacq, Christophe; Peremans, T.; Kerkhofs, Pierre et al

in Aids Research and Human Retroviruses": 10th International Conference on Human Retrovirology: HTLV and Related Viruses, (2001, June)

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See detailA critical cysteine residue of bovine leukemia virus SU protein interacts with zinc and plays a role in viral infectivity.
Gatot, Jean-Stéphane; Kerkhofs, Pierre; Burny, Arsène et al

in The 2001 meeting on Retroviruses. (2001, May)

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See detailCell turnover in BLV-infected sheep.
Debacq, C.; Peremans, T.; Kerkhofs, P. et al

in AIDS Research and Human Retroviruses (2001), 17(1), 13

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